Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

• Published in: Nature communications 2020-03, Vol.11 (1), p.1453-1453, Article 1453
• Main Authors: Paul, Sarika, Hanna, Lydia, Harding, Court, Hayter, Edward A., Walmsley, Lauren, Bechtold, David A., Brown, Timothy M.
• Format: Article
• Language: English
• Subjects: 14/1; 14/35; 42/44; 631/378/1385/2640; 631/378/3920; 64/60; Action Potentials - drug effects; Action Potentials - physiology; Animals; Bicuculline - pharmacology; Biological clocks; Channelrhodopsins - chemistry; Channelrhodopsins - genetics; Channelrhodopsins - metabolism; Circadian Clocks - drug effects; Circadian Clocks - physiology; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Circuits; Communication; Corticosterone; Corticosterone - blood; Corticosterone - metabolism; Electrodes, Implanted; Female; GABA-A Receptor Antagonists - pharmacology; GABAergic Neurons - drug effects; GABAergic Neurons - metabolism; Heart rate; Heart Rate - physiology; Humanities and Social Sciences; Hypothalamus; Information systems; Intestine; Male; Mammals; Mice; Mice, Transgenic; Models, Animal; multidisciplinary; Neurons; Physiology; Polypeptides; Regulators; Science; Science (multidisciplinary); Suprachiasmatic nucleus; Suprachiasmatic Nucleus - cytology; Suprachiasmatic Nucleus - physiology; Thalamus; Vasoactive agents; Vasoactive intestinal peptide; Vasoactive Intestinal Peptide - antagonists & inhibitors; Vasoactive Intestinal Peptide - genetics; Vasoactive Intestinal Peptide - metabolism; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15277-x

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing. VIP-expressing neurons play a central role in circadian timekeeping within the mammalian central clock. Here the authors use opto- and chemogenetic approaches to show that VIP neuronal activity regulates rhythmic activity in downstream hypothalamic target neurons and their physiological functions.